This project deals with the identification and molecular characterization of dominant oncogenes present in human tumor cell lines and in naturally occurring tumors. A common oncogene, related to the Kirsten strain of murine sarcoma virus (MSV), has been detected frequently in a variety of human tumor cell lines and solid tumors including carcinomas of the lung, pancreas and an embryonal rhabdomyosarcoma. Particular findings dealing with the T24 bladder carcinoma oncogene include: (1) the T24 oncogene as an activated allele of the c-has/bas-1 human protooncogene; (2) comparative sequence analysis of both alleles shows that a single point mutation (a G to T transversion) leading to the substitution of valine for glycine as the twelfth amino acid residue of its gene product (designed p21) is reponsible for the malignant properties of the T24 oncogene; (3) the normal allele of the T24 oncogene has been mapped to human chromosome 11; (4) a spontaneous transforming mutant of the normal allele that arose during transfection experiments has also been cloned; (5) analysis of the nucleotide sequence of this mutant reveals the occurrence of a different point mutation (a G to A transition) at the same position of that found in the T24 oncogene, this time leading to substitution of aspartic acid for glycine at position 12 of the amino acid sequence. Current projects involve molecular studies dealing with the Kirsten-related oncogene frequently detected in a variety of human tumors.